The purpose of this amended Phase I study will be to evaluate the safety and toxicity of escalating doses of intravenous ganciclovir (GCV) coupled with intrapleural delivery of a "third generation" El/E4-deleted adenoviral vector expressing the Herpes Simplex Thymidine kinase (HSVtk) gene to treat patients with inoperable malignant mesothelioma. This study is a logical extension of our past and present Phase l studies evaluating the safety and toxicity of escalating doses of intrapleural recombinant adenoviral-HSV tk vector in combination with intravenous GCV to treat patients with mesothelioma.